Summary Safety Review - Vitamin B6 Health Products - Assessing the Potential Risk of Peripheral Neuropathy

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Products
Vitamin B6-containing heath products (natural health products [NHPs] and prescription drugs), with a daily dose of 10 mg vitamin B6 or higher
Potential Safety Issue
Peripheral neuropathy (damage to or disease affecting peripheral nerves)
Key Messages

  • Health Canada’s review found a possible link between vitamin B6-containing NHPs and the risk of peripheral neuropathy, when taken at daily doses of 10 mg vitamin B6 or higher.

  • Health Canada’s review did not find sufficient evidence to establish a link between vitamin B6-containing prescription drugs and the risk of peripheral neuropathy, despite these products containing similar amounts of vitamin B6 to what is found in NHPs.

  • Health Canada will update the monographa,b for vitamin B6-containing NHPs to include the risk of peripheral neuropathy. Health Canada expects license holders to update the risk information on product labels for all licensed vitamin B6-containing NHPs with a daily dose of 10 mg vitamin B6 or higher to:

    • include information about the warning signs and symptoms of peripheral neuropathy, including sensory nerve problems (numbness, tingling and pain in the extremities), and

    • advise consumers to stop using these NHPs and consult a healthcare professional if these symptoms occur. 

  • Health Canada does not recommend an update to the product safety information in the Canadian product monograph (CPM) for vitamin B6-containing prescription drugs at this time, as standardized prescription practices and monitoring of pregnant patients by healthcare professionals are already in place.

  • Health Canada will also inform healthcare professionals and consumers about these updates through a Health Product InfoWatch communication and a social media campaign.

Overview

Vitamin B6, also known as pyridoxine, pyridoxamine, pyridoxal and their phosphate derivatives (chemical compounds derived from phosphoric acid), is naturally found in many foods, added to others (supplemented foods and fortified foods), and available as a health product (NHPs and prescription drugs).

When consumed in high amounts (250 mg vitamin B6/day and above), vitamin B6-containing health products may cause peripheral neuropathy.1 In recent years, however, evidence has suggested that peripheral neuropathy may also be associated with lower doses, which are within the dose range of vitamin B6-containing health products (NHPs and prescription drugs) currently marketed in Canada.

In 2024, Health Canada reviewed this potential risk with the use of vitamin B6-containing NHPs. This safety review was triggered by a scientific study reporting international cases of peripheral neuropathy associated with the use of vitamin B6 health products for daily doses under 100 mg2, and after reviewing assessments completed by foreign regulatory agencies (Australia’s Therapeutic Goods Administration [TGA], Netherlands Pharmacovigilance Centre Lareb and the European Food Safety Authority [EFSA]).

In 2025, Health Canada also reviewed the potential risk of peripheral neuropathy with the use of vitamin B6-containing prescription drugs to determine if additional risk mitigation measures were needed for these types of products.

Supplemented foods, including caffeinated energy drinks, were not included as part of these reviews and the use of vitamin B6 in these foods is reviewed separately. However, consumers should note that these products may also contain higher amounts of added vitamin B6, similar to NHPs.

Vitamin B6 that is naturally found in whole foods, and vitamin B6 in fortified foods such as breakfast cereals, have not been identified as a safety concern and were not included as part of these reviews.

Use in Canada

  • Vitamin B6 is authorized in Canada for use in NHPs, typically to help in energy metabolism and tissue formation, form red blood cells, prevent vitamin B6 deficiency, and maintain/support the body's ability to metabolize (process) nutrients. Over 4,000 vitamin B6-containing NHPs have been authorized by Health Canada under the Natural Health Products Regulations with recommended daily doses of 10 mg vitamin B6 or higher.

  • Prescription drugs that contain vitamin B6 are authorized for sale in Canada for the treatment of nausea and vomiting in pregnancy under the brand name Diclectin (pyridoxine/doxylamine), or for use as a pregnancy multivitamin under the brand names Pregvit and Pregvit Folic 5. Generic versions are also available. Every year, approximately 230,000 new prescriptions for vitamin B6-containing drugs are filled in Canada.

  • Vitamin B6-containing health products have been marketed in Canada for over 20 years.

Safety Review Findings

  • Health Canada reviewed the available information provided by foreign regulatory agencies, as well as from searches of the Canada Vigilance databasec, international databases and the scientific literature.

  • At the time of the reviews, Health Canada identified 17 cases (15 Canadian and 2 international) of peripheral neuropathy in patients taking either vitamin B6-containing NHPs (14 cases) or vitamin B6-containing prescription drugs (3 cases). However, 15 of the 17 cases did not meet the criteria for further assessment to determine if there was a link. Though in the 2 remaining cases, which were in patients using vitamin B6-containing NHPs, further assessment was limited due to missing clinical information and the presence of confounders (other factors that may have contributed to the occurrence of peripheral neuropathy), such as the use of other supplements, the potential risk of peripheral neuropathy cannot be excluded.

  • Health Canada also reviewed 9 articles published in the scientific literature, which supported a possible link between the use of vitamin B6-containing health products at daily doses as low as 10 mg vitamin B6 and the risk of peripheral neuropathy.2-10 Currently, no well characterized risk factors for developing peripheral neuropathy while using vitamin B6-containing health products have been identified.

  • Both foreign regulatory agencies11-12 and international pharmacovigilance groups13-14 have identified cases of neuropathy with the use of vitamin B6-containing health products and, in some cases, established a possible link between peripheral neuropathy and vitamin B6-containing health products. Among the actions taken in response to their findings are:

    • The TGA’s implementation of label updates for vitamin B6-containing health products to include the risk of peripheral neuropathy when the daily dose is over 10 mg of vitamin B6.11-12

    • The EFSA’s recommendation to lower the tolerable upper intake level of vitamin B6 to 12 mg/day for foods.13

Conclusions and Actions

  • Health Canada’s review found a possible link between vitamin B6-containing NHPs and the risk of peripheral neuropathy, when the daily dose is 10 mg vitamin B6 or higher.

  • Health Canada will update the monograph for vitamin B6-containing NHPs to include the risk of peripheral neuropathy. Health Canada expects license holders to update the risk information on product labels for all licensed vitamin B6-containing NHPs with a daily dose of 10 mg vitamin B6 or higher to:

    • include information about the warning signs and symptoms of peripheral neuropathy, including sensory nerve problems (numbness, tingling and pain in the extremities), and

    • advise consumers to stop using these NHPs and consult a healthcare professional if symptoms occur. 

  • Health Canada’s review did not find sufficient evidence to establish a link between vitamin B6-containing prescription drugs and the risk of peripheral neuropathy despite these products containing similar amounts of vitamin B6 to what is found in NHPs.

  • Health Canada does not recommend an update to the product safety information in the CPM for vitamin B6-containing prescription drugs at this time, as standardized prescription practices and monitoring of pregnant patients by healthcare professionals are already in place.

  • Health Canada will also inform healthcare professionals and consumers about these updates through a Health Product InfoWatch communication and a social media campaign.

  • Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of vitamin B6-containing health products (NHPs and prescription drugs), and other health products, to the Canada Vigilance Program.

  • Health Canada will continue to monitor safety information involving vitamin B6-containing products (NHPs and prescription drugs), as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of vitamin B6 both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Hemminger A, Wills BK. Vitamin B6 Toxicity. [Updated 2023 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554500/

  2. van Hunsel F, van de Koppel S, van Puijenbroek E, Kant A. Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases. Drug Saf. 2018;41(9):859-869. doi:10.1007/s40264-018-0664-0

  3. Muhamad R, Akrivaki A, Papagiannopoulou G, Zavridis P, Zis P. The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review. Nutrients. 2023;15(13):2823. 2023doi:10.3390/nu15132823

  4. Visser NA, Notermans NC, Degen LA, de Kruijk JR, van den Berg LH, Vrancken AF. Chronic idiopathic axonal polyneuropathy and vitamin B6: a controlled population-based study. J Peripher Nerv Syst. 2014;19(2):136-144. doi:10.1111/jns5.12063

  5. Stewart SL, Thomas S, Höke E, Simpson D, Singleton JR, Höke A. Vitamin B6 levels do not correlate with severity of neuropathy in chronic idiopathic axonal polyneuropathy. J Peripher Nerv Syst. 2022;27(1):31-37. doi:10.1111/jns.12480

  6. Ghavanini AA, Kimpinski K. Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess. J Clin Neuromuscul Dis. 2014;16(1):25-31. doi:10.1097/CND.0000000000000049

  7. Kulkantrakorn K. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited. Neurol Sci. 2014;35(11):1827-1830. doi:10.1007/s10072-014-1902-6

  8. Paluszny A, Qiu S. Vitamin B6 Toxicity Secondary to Daily Multivitamin Use: A Case Report. Cureus. 2023;15(11):e48792. Published 2023 Nov 14. doi:10.7759/cureus.48792

  9. Malet L, Dayot L, Moussy M, de la Gastine B, Goutelle S. Neuropathie périphérique avec hypervitaminose B6 provoquée par l’automédication [Peripheral neuropathy with hypervitaminosis B6 caused by self medication]. Rev Med Interne. 2019;41(2):126-129. doi:10.1016/j.revmed.2019.11.003

  10. Sista SRS, Lozowska D, Katzin LW, Vu TH. Multivitamin supplements and energy drinks in pyridoxine megavitaminosis. Neurol Clin Pract. 2015;5(6):509-511. doi:10.1212/CPJ.0000000000000142

  11. TGA. Proposed changes to requirements for listed medicine ingredients: Annual low-negligible risk changes 2021-2021-Final Decisions. Published December 2021. Accessed January 16th, 2026. Low-negligible risk annual consultation 2021-2022 - Final Decisions.pdf

  12. TGA. Peripheral Neuropathy with supplementary vitamin B6 (pyridoxin). Published October 4th, 2022. Accessed January 16th, 2026. Adverse events reported to the TGA and overseas | Peripheral neuropathy with supplementary vitamin B6 (pyridoxine) | Therapeutic Goods Administration (TGA)

  13. EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, et al. Scientific opinion on the tolerable upper intake level for vitamin B6. EFSA J. 2023;21(5):e08006. Published 2023 May 17. doi:10.2903/j.efsa.2023.8006

  14. Netherlands pharmacovigilance centre Lareb. Nerve damage due to the use of nutritional supplements. Published November 13th, 2024. Accessed January 16th, 2026. https://www.lareb.nl/en/news/nerve-damage-due-to-the-use-of-nutritional-supplements-with-vitamin-b6/

Footnotes

  1. Monographs and product monographs are a written description of particular elements on an identified topic. In the case of NHPs, a monograph is specific to an individual ingredient or a combination of ingredients that are authorized for use in NHPs sold in Canada. In the case of drugs, product monographs are specific to a particular drug product authorized for sale in Canada.

  2. Monographs for NHP ingredients can be accessed through the Compendium of monographs.

  3. Canadian reports can be accessed through the Canada Vigilance Online Database.

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